JP5113057B2 - Lipid metabolism improver - Google Patents
Lipid metabolism improver Download PDFInfo
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Description
技術分野
[0001]
本発明は、バチルス属の細菌、特にバチルス・ズブチリスC−3102株の菌体またはその培養物を有効成分とする、血清トリグリセライド値を低下させる作用を有する脂質代謝改善剤に関する。
背景技術
[0002]
血清のトリグリセライド値の上昇は、高脂血症、動脈硬化症、虚血性心疾患(狭心症や心筋こうそく)、また糖尿病などを発症する原因でもあり、一般的に生活習慣病の指標となっている。また食後の中性脂肪の増加やその持続が、循環器系疾患に最も影響する因子であることがわかっている。
[0003]
一般に高脂血症の治療には、薬物療法と脂質摂取量を制限した食事療法が行われる。薬物療法には、コレステロール合成経路の3−ヒドロキシ−3−メチルグルタリル補酵素A(HMG−CoA)よりメバロン酸への合成を阻害することによりコレステロール生合成を阻害するHMG−CoAリダクターゼ阻害剤や胆汁酸吸着剤(陰イオン交換樹脂)などの薬物が用いられている。
[0004]
しかしながらHMG−CoAリダクターゼ阻害剤は、過敏症や肝機能異常、横紋筋融解症等の副作用を有する。またコレスチラミンなどの陰イオン交換樹脂を用いると、陰イオン交換樹脂が消化管内でコレステロールを多く含む胆汁酸を吸着してその腸肝循環を遮断し、コレステロールを体外に排泄させるが、投与量が多く飲みにくくかつ便秘や消化管症状を引き起こす等の問題がある。また、食事療法は食事制限による精神的苦痛を伴うので、長期間にわたって継続的に実施することは困難である。
[0005]
したがって副作用が無く継続的に摂取しやすい、血清トリグリセライド低下作用を有する薬剤ならびに食品が求められている。
特許文献1:特公平4−24022
発明の開示
発明が解決しようとする課題
【0006】
本発明の目的は、動脈硬化症などの疾患の治療および予防に有用な脂質代謝改善剤を提供することにある。
【課題を解決するための手段】
【0007】
本発明は、バチルス属に属する細菌の菌体または培養物を有効成分とする脂質代謝改善剤を提供する。本発明はまた、バチルス属に属する細菌の菌体または培養物を有効成分とする血清トリグリセライド値低下剤を提供する。好ましくは、バチルス属に属する細菌はバチルス・ズブチリスであり、より好ましくはバチルス・ズブチリスC−3102(FERM BP-1096)である。
【図面の簡単な説明】
【0008】
【図1】図1は、バチルス・ズブチリスC−3102株ゲノムDNAの制限酵素NotIまたはSfiI消化パターンを示す。
【図2】図2は、本発明の脂質代謝改善剤を摂取した被験者の血清トリグリセライド濃度の推移を示す。
【発明を実施するための最良の形態】
【0009】
バチルス属の菌(例えば、Bacillus subtilis)は古くからヒトの食生活に深くかかわっており、その機能性についての情報は多いが、血清トリグリセライドの低下作用や脂質代謝改善効果があることは未だ報告されていない。
【0010】
本発明の脂質代謝改善剤および血清トリグリセライド値低下剤は、バチルス属に属する細菌の菌体またはその培養物、好ましくはバチルス・ズブチリス(Bacillus subtilis)の菌体またはその培養物を有効成分として含むことを特徴とする。バチルス・ズブチリスの菌学的性質はバージーズ・マニュアル・オブ・バクテリオロジー Vol.11(1986)等に記載されており、具体的には例えば以下の特徴を有する。
(1)グラム陽性
(2)卵円形の芽胞を形成
(3)桿菌
(4)運動性:あり
(5)好気性
(6)カタラーゼ:陽性
(7)50℃における発育:+
(8)pH5.7における発育:+
(9)クエン酸塩の利用:+
(10)糖類からの酸生成の有無:アラビノース、グルコース、キシロース、マンニット:+
(11)VP反応:+
(12)デンプンの加水分解:+
(13)硝酸塩の還元性:+
(14)インドールの生成:−
(15)ゼラチンの加水分解:+
(16)カゼインの加水分解:+
(17)液体培地での被膜形成:+
(18)牛乳の凝固:−
(19)牛乳のペプトン化:+
【0011】
本発明の脂質代謝改善剤および血清トリグリセライド値低下剤に用いるバチルス・ズブチリスとしては、例えば、バチルス・ズブチリスC−3102株(生命工学工業技術研究所寄託番号 FERM BP−1096、寄託日1985年12月25日)を挙げることができる。バチルス・ズブチリスC-3102株の大豆培養物は家畜に対して、腸内細菌叢改善、増体、感染防御、卵殻強化、肉質改善、便臭改善等の効果があり、添加物として利用されている(特公平4−24022)。またこの株の保健効果として、整腸作用、腸内腐敗産物の減少などが知られている。(腸内細菌学会誌 第18巻 第二号 93-99(2004))。
【0012】
バチルス・ズブチリスC−3102は、下記配列1及び配列2のPCRプライマーを用いてPCR反応を行うと約700bpsの断片が増幅するという特徴を持つ。他のバチルス・ズブチリスでは、このPCRプライマーによっては増幅は起こらない。バチルス・ズブチリスC−3102のゲノムをテンプレートとして増幅される約700bpsの断片は、アミラーゼの配列と相同性を有しないという特徴をもち、この点においてC−3102株はバチルス・ズブチリスの他の株と明確に識別される。
配列1:5’−GCCCCGCACATACGAAAAGACTGGCTGAAA−3’(配列番号1)
配列2:5’−GGATCCCACGTTGTGATTAAAAGCAGCGAT−3’(配列番号2)
さらに、バチルス・ズブチリスC−3102株は以下の性質を有する:
(1)プラスミドDNAを有しない。
(2)ゲノムDNAを調製し、制限酵素NotIまたはSfiIで消化してアガロース電気泳動により分離したときの消化パターンは図1に示されるとおりである。
(3)B.cerous抗菌物質を産生する。
(4)アンピシリン、クロラムフェニコール、シプロフロキサシン、エリスロマイシン、ゲンタマイシン、カナマイシン、リネゾリド、キヌプリスチン/ダルフォプリスチン、リファムピン、ストレプトマイシン、テトラサイクリン、トリメトプリム、バンコマイシンに対して耐性を有しない(いずれも最小阻害濃度0.03〜4μg/ml)。
【0013】
バチルス・ズブチリスは、培地として微生物培養に通常使用される炭素源、窒素源、無機物等を含む液体培地又は固体培地を用いて培養することができる。炭素源としては、バチルス・ズブチリスが資化可能な炭素源であればよく、例えばグルコース、フルクトース、スクロース、スターチ、糖蜜等を、また窒素源としては、例えばペプトン、カゼイン加水分解物、肉エキス、硫安等を挙げることができる。更に、必要に応じて燐酸、カリウム、マグネシウム、カルシウム、ナトリウム、鉄およびマンガン等の塩類、ビタミン類、アミノ酸類、界面活性剤等を添加することもできる。また、これらの合成培地の他、大豆油かすなどの天然物由来物質を用いて培養してもよい。培養条件としては、好気的条件が好ましく、培養装置としては例えばジャーファーメンターによる通気撹拌液体培養、棚式固体培養、自動製麹培養装置等が好ましい。培養温度は20〜50℃、特に30〜45℃が好ましく、培養時間は12時間〜7日間、培養初発pHはpH5〜9、特に好ましくはpH6〜8である。
【0014】
このようにして得られた培養物は、バチルス・ズブチリスの菌体、培地および発酵生成物を含む。培養物は、脂質代謝改善剤またはトリグリセライド低下剤としてそのまま用いてもよく、培養物を濃縮してもよく、またはこれらに賦形剤等を加えて乾燥粉末、顆粒、錠剤等の製剤として用いてもよい。また、培養物から分離した菌体を用いてもよく、培養物から菌体を除去して用いてもよく、菌体を含む形の培養物を用いてもよい。特に好ましい態様においては、バチルス・ズブチリスは、大豆油かす、大豆煮豆、小豆煮豆、米飯、麦飯、小麦ふすま、煮とうもろこし、その他の穀類などの食用に適した天然物由来物質を用いて培養し、培養物から菌体を分離することなく、そのまま食品に配合する。
【0015】
本発明の脂質代謝改善剤および血清トリグリセライド値低下剤は、液体、粉末、造粒物、錠剤等の形で投与してもよく、食品添加物として飲食品中に配合して摂取してもよい。飲食品としては、例えば、飲料、製菓錠菓、ペースト、パン、魚肉加工製品、乳製品などが挙げられる。本発明の脂質代謝改善剤および血清トリグリセライド値低下剤をこれらの様々な食品素材に添加して、健康飲料、健康食品あるいは機能性食品として提供することができる。
【0016】
以上記述したとおり、本発明はバチルス・ズブチリスの菌体またはその培養物を有効成分とする血清トリグリセライド低下効果のある脂質代謝改善剤に関するものである。本発明の有効成分であるバチルス・ズブチリスは微量かつ短期間で有効であり、保存性と耐酸性にもすぐれ腸内に到達して増殖しやすく、持続的な血清トリグリセライドの低下作用が期待できる。
【0017】
本明細書において明示的に引用される全ての特許および参考文献の内容は全て参照により本明細書に取り込まれる。また,本出願が有する優先権主張の基礎となる出願である日本特許出願2006-224672号の明細書および図面に記載の内容は全て参照により本明細書に取り込まれる。
【0018】
以下に実施例により本発明をより詳細に説明するが,これらの実施例は本発明の範囲を制限するものではない。
【実施例1】
【0019】
以下の実施例においては、バチルス属に属する細菌の例として、バチルス・ズブチリスC−3102株(生命工学工業技術研究所寄託番号 FERM BP−1096、寄託日1985年12月25日)を用いた。
【0020】
市販大豆油かす造粒品5kgに水道水5kgを加えて121℃、120分間殺菌し、予め前培養しておいたバチルス・ズブチリスC-3102株の培養液を接種し、37℃、40時間培養することにより、バチルス・ズブチリスC-3102株の大豆培養物を製造した。このようにして得られた培養物を乾燥粉砕し、下記の表に示す他の成分を配合して、1錠約500mg(3×109個のバチルス・ズブチリス胞子を含む)の錠剤を製造した。錠剤の栄養成分を表1-1、組成を表1-2に示す。
【0021】
【表1】
【実施例2】
【0022】
血清トリグリセライド上昇抑制試験(ヒト摂食試験の実施)
試験方法
【0023】
年齢が25歳から40歳までの健康な男女10名(女性5名、男性5名)を被験者とした。選定基準を表2に示す。なお、特定の薬剤または特定保健用食品を投与または摂取している者は除外した。
[0024]
[表2]
[0025]
被験者は、1日1回1錠500mg(3×109の胞子を含むBacillus subtilis C−3102株大豆培養物の錠剤)を、可能な限り朝食後に、4週間経口摂取した。摂食開始前、摂食1週間後、2週間後、3週間後、4週間後に、空腹時(前日の夜9時以降の飲食禁止、午前中の採血時間は定時とした)に採血し、血清トリグリセライド値を測定した。試験スケジュールを表3に示す。
[0026]
[表3]
【0027】
上記試験の結果を図2に示す。血清トリグリセライドの推移は、摂取開始時103.6±42.82mg/dl、摂取1週間後69.8±32.00mg/dl、摂取2週間後63.0±24.58 mg/dl、摂取3週間後77.0±35.63 mg/dl、摂取4週間後71.8±37.26 mg/dlであった。摂取期間による反復測定一元配置分散分析の結果、有意な差(p<0.01)が認められた。多重比較(Tukey-Kraner検定)の結果、摂取開始時と摂取1週間後の間(p<0.05)、摂取開始時と摂取2週間後の間(p<0.05)、摂取開始時と摂取4週間後の間(p<0.05)に有意な差が認められた。以上の結果から、バチルス・ズブチリスC-3102株大豆培養物は、血清トリグリセライドの低下作用を有することが明らかとなった。
【産業上の利用可能性】
【0028】
本発明の脂質代謝改善剤は、ヒトが摂食することにより血清トリグリセライド濃度を低下させることができ、動脈硬化症の予防・改善剤として有用である。Technical field [0001]
The present invention relates to a lipid metabolism-improving agent having an action of lowering serum triglyceride level, comprising as an active ingredient a bacterium belonging to the genus Bacillus, particularly a cell of Bacillus subtilis strain C-3102 or a culture thereof.
Background art [0002]
An increase in serum triglyceride levels is also a cause of developing hyperlipidemia, arteriosclerosis, ischemic heart disease (angina and myocardial infarction), and diabetes, and is generally an indicator of lifestyle-related diseases ing. In addition, it has been found that the increase and persistence of neutral fat after meals are the most influential factors for cardiovascular diseases.
[0003]
In general, for treatment of hyperlipidemia, drug therapy and diet therapy with limited lipid intake are performed. For drug therapy, an HMG-CoA reductase inhibitor that inhibits cholesterol biosynthesis by inhibiting synthesis of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonic acid in the cholesterol synthesis pathway , Drugs such as bile acid adsorbents (anion exchange resins) are used.
[0004]
However, HMG-CoA reductase inhibitors have side effects such as hypersensitivity, liver function abnormality, and rhabdomyolysis. In addition, when an anion exchange resin such as cholestyramine is used, the anion exchange resin adsorbs bile acids containing a large amount of cholesterol in the digestive tract, blocks its enterohepatic circulation, and excretes cholesterol outside the body. It is difficult to drink and causes problems such as constipation and gastrointestinal symptoms. In addition, dietary therapy is accompanied by mental distress due to dietary restrictions, so it is difficult to continue for a long time.
[0005]
Accordingly, there is a need for drugs and foods that have an effect of lowering serum triglycerides, which have no side effects and are easily taken continuously.
Patent Document 1: Japanese Patent Publication No. 4-24022
DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention
An object of the present invention is to provide a lipid metabolism improving agent useful for the treatment and prevention of diseases such as arteriosclerosis.
[Means for Solving the Problems]
[0007]
The present invention provides a lipid metabolism improving agent comprising a bacterial cell or culture belonging to the genus Bacillus as an active ingredient. The present invention also provides a serum triglyceride level-lowering agent comprising a bacterial cell or culture belonging to the genus Bacillus as an active ingredient. Preferably, the bacterium belonging to the genus Bacillus is Bacillus subtilis, more preferably Bacillus subtilis C-3102 (FERM BP-1096).
[Brief description of the drawings]
[0008]
FIG. 1 shows a restriction enzyme NotI or SfiI digestion pattern of Bacillus subtilis C-3102 strain genomic DNA.
FIG. 2 shows the transition of serum triglyceride concentration in subjects who took the lipid metabolism improving agent of the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
[0009]
Bacillus subtilis (for example, Bacillus subtilis) has long been deeply involved in human diet, and there is much information on its functionality, but it has been reported that it has a lowering effect on serum triglycerides and an effect on improving lipid metabolism. Not.
[0010]
The lipid metabolism-improving agent and serum triglyceride level-lowering agent of the present invention comprise a bacterial cell belonging to the genus Bacillus or a culture thereof, preferably a Bacillus subtilis bacterial cell or a culture thereof as an active ingredient. It is characterized by. The bacteriological properties of Bacillus subtilis are described in Birge's Manual of Bacteriology Vol. 11 (1986), etc., and specifically has the following characteristics, for example.
(1) Gram positive (2) Oval spore formation (3) Neisseria gonorrhoeae (4) Motility: Yes (5) Aerobic (6) Catalase: Positive (7) Growth at 50 ° C: +
(8) Growth at pH 5.7: +
(9) Use of citrate: +
(10) Presence or absence of acid generation from sugars: arabinose, glucose, xylose, mannitol: +
(11) VP reaction: +
(12) Starch hydrolysis: +
(13) Reduction of nitrate: +
(14) Production of indole: −
(15) Gelatin hydrolysis: +
(16) Casein hydrolysis: +
(17) Film formation in liquid medium: +
(18) Milk coagulation:-
(19) Milk peptone: +
[0011]
Examples of the Bacillus subtilis used in the lipid metabolism improving agent and the serum triglyceride level reducing agent of the present invention include, for example, Bacillus subtilis C-3102 strain (Deposit number FERM BP-1096, Biotechnology Institute of Technology, Deposit date: December 1985) 25th). The soy culture of Bacillus subtilis strain C-3102 has effects such as improving intestinal microflora, increasing body weight, protecting against infection, strengthening eggshell, improving meat quality, and improving stool odor. (Japanese Patent Publication No. 4-24022). In addition, as a health effect of this strain, it is known that the intestinal regulating action, the reduction of intestinal rot products, etc. (Journal of Intestinal Bacteria Vol.18, No.2, 93-99 (2004)).
[0012]
Bacillus subtilis C-3102 is characterized in that a fragment of about 700 bps is amplified when PCR reaction is performed using PCR primers of the following
Sequence 1: 5′-GCCCCGCACATACGAAAAGACTGGCTGAAA-3 ′ (SEQ ID NO: 1)
Sequence 2: 5′-GGATCCCACGTTGGTATTAAAAGCAGCGAT-3 ′ (SEQ ID NO: 2)
Further, Bacillus subtilis C-3102 strain has the following properties:
(1) Does not have plasmid DNA.
(2) The digestion pattern when genomic DNA is prepared, digested with restriction enzymes NotI or SfiI and separated by agarose electrophoresis is as shown in FIG.
(3) Produces B.cerous antibacterial substances.
(4) Not resistant to ampicillin, chloramphenicol, ciprofloxacin, erythromycin, gentamicin, kanamycin, linezolid, quinupristin / dalfopristin, rifapampine, streptomycin, tetracycline, trimethoprim, vancomycin Inhibitory concentration 0.03-4 μg / ml).
[0013]
Bacillus subtilis can be cultured using a liquid medium or a solid medium containing a carbon source, a nitrogen source, an inorganic substance and the like that are usually used for culturing microorganisms. The carbon source may be any carbon source that can assimilate Bacillus subtilis, for example, glucose, fructose, sucrose, starch, molasses, etc., and the nitrogen source, for example, peptone, casein hydrolyzate, meat extract, An ammonium sulfate etc. can be mentioned. Furthermore, salts such as phosphoric acid, potassium, magnesium, calcium, sodium, iron and manganese, vitamins, amino acids, surfactants and the like can be added as necessary. Moreover, you may culture | cultivate using natural product origin substances, such as soybean oil residue other than these synthetic culture media. The culture condition is preferably an aerobic condition, and the culture apparatus is preferably, for example, an aeration and agitation liquid culture using a jar fermenter, a shelf-type solid culture, or an automatic koji culture apparatus. The culture temperature is preferably 20 to 50 ° C., particularly preferably 30 to 45 ° C., the culture time is 12 hours to 7 days, and the initial culture pH is pH 5 to 9, particularly preferably pH 6 to 8.
[0014]
The culture obtained in this way contains B. subtilis cells, media and fermentation products. The culture may be used as it is as a lipid metabolism improving agent or triglyceride reducing agent, or the culture may be concentrated, or an excipient or the like may be added to these to be used as a preparation such as a dry powder, granule or tablet. Also good. Moreover, the microbial cell isolate | separated from the culture may be used, a microbial cell may be removed from a culture, and it may be used, and the culture of the form containing a microbial cell may be used. In a particularly preferred embodiment, Bacillus subtilis is cultured using edible natural substances derived from edible products such as soybean meal, soybean boiled beans, red beans boiled beans, cooked rice, barley rice, wheat bran, boiled corn, and other grains. It mix | blends with food as it is, without isolate | separating a microbial cell from a culture.
[0015]
The lipid metabolism-improving agent and serum triglyceride level-lowering agent of the present invention may be administered in the form of a liquid, powder, granulated product, tablet, etc., or may be ingested as a food additive in foods and drinks. . Examples of the food and drink include beverages, confectionery tablets, pastes, breads, processed fish products, and dairy products. The lipid metabolism-improving agent and serum triglyceride level-lowering agent of the present invention can be added to these various food materials to provide health drinks, health foods or functional foods.
[0016]
As described above, the present invention relates to a lipid metabolism improving agent having an effect of lowering serum triglyceride, which comprises a Bacillus subtilis cell or a culture thereof as an active ingredient. Bacillus subtilis which is an active ingredient of the present invention is effective in a trace amount and in a short period of time, has excellent storage stability and acid resistance, easily reaches the intestine and proliferates, and can be expected to have a continuous lowering effect on serum triglyceride.
[0017]
The contents of all patents and references explicitly cited herein are hereby incorporated by reference. In addition, the contents described in the specification and drawings of Japanese Patent Application No. 2006-224672, which is the application on which the priority of the present application is based, are incorporated herein by reference.
[0018]
The present invention will be described in more detail with reference to the following examples, but these examples do not limit the scope of the present invention.
[Example 1]
[0019]
In the following examples, Bacillus subtilis C-3102 strain (Deposit number FERM BP-1096, deposit date December 25, 1985) was used as an example of bacteria belonging to the genus Bacillus.
[0020]
Add 5 kg of tap water to 5 kg of commercial soybean oil granulated product, sterilize at 121 ° C for 120 minutes, inoculate the pre-cultured Bacillus subtilis C-3102 strain, and culture at 37 ° C for 40 hours As a result, a soybean culture of Bacillus subtilis strain C-3102 was produced. The culture thus obtained was dried and ground and blended with other ingredients shown in the following table to produce a tablet of about 500 mg (including 3 × 10 9 Bacillus subtilis spores). . Table 1-1 shows the nutritional components of the tablet, and Table 1-2 shows the composition.
[0021]
[Table 1]
[Example 2]
[0022]
Serum triglyceride elevation suppression test (Human feeding test)
Test method [0023]
The subjects were 10 healthy men and women (5 women and 5 men) aged 25 to 40 years. Table 2 shows the selection criteria. Excluded were those who were taking or taking specific drugs or foods for specified health use.
[0024]
[Table 2]
[0025]
The subjects took 1 tablet 500 mg (tablet of Bacillus subtilis C-3102 soybean culture containing 3 × 10 9 spores) orally once daily after breakfast for 4 weeks. Feeding before the start, eating after one week, after two weeks, three weeks later, after 4 weeks, fasting (of the night 9:00 later of the day before eating and drinking ban, it was a punctual blood collection time in the morning) and bled, Serum triglyceride values were measured. The test schedule is shown in Table 3.
[0026]
[Table 3]
[0027]
The results of the above test are shown in FIG. Changes in serum triglyceride were 103.6 ± 42.82 mg / dl at the start of ingestion, 69.8 ± 32.00 mg / dl after 1 week of ingestion, 63.0 ± 24.58 mg / dl after 2 weeks of ingestion, 77.0 ± 35.63 mg / dl after 3 weeks of ingestion, ingestion After 4 weeks, the dose was 71.8 ± 37.26 mg / dl. As a result of repeated one-way analysis of variance based on the intake period, a significant difference (p <0.01) was observed. As a result of multiple comparisons (Tukey-Kraner test), the results were as follows: between the start of intake and 1 week after intake (p <0.05), between the start of intake and 2 weeks after intake (p <0.05), at the start of intake and 4 weeks after intake There was a significant difference between later (p <0.05). From the above results, it was revealed that the soybean culture of Bacillus subtilis strain C-3102 has an effect of lowering serum triglyceride.
[Industrial applicability]
[0028]
The lipid metabolism-improving agent of the present invention can lower serum triglyceride concentration by human consumption, and is useful as a prophylactic / ameliorating agent for arteriosclerosis.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008530867A JP5113057B2 (en) | 2006-08-21 | 2007-08-14 | Lipid metabolism improver |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006224672 | 2006-08-21 | ||
| JP2006224672 | 2006-08-21 | ||
| PCT/JP2007/065848 WO2008023608A1 (en) | 2006-08-21 | 2007-08-14 | Lipid-metabolism-ameliorating agent |
| JP2008530867A JP5113057B2 (en) | 2006-08-21 | 2007-08-14 | Lipid metabolism improver |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPWO2008023608A1 JPWO2008023608A1 (en) | 2010-01-07 |
| JP5113057B2 true JP5113057B2 (en) | 2013-01-09 |
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| JP2008530867A Active JP5113057B2 (en) | 2006-08-21 | 2007-08-14 | Lipid metabolism improver |
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| US (2) | US20100183576A1 (en) |
| EP (1) | EP2060263A4 (en) |
| JP (1) | JP5113057B2 (en) |
| KR (1) | KR101454228B1 (en) |
| CN (1) | CN101511377B (en) |
| BR (1) | BRPI0715740A8 (en) |
| CA (1) | CA2661373C (en) |
| MX (1) | MX2009001782A (en) |
| TW (1) | TW200817020A (en) |
| WO (1) | WO2008023608A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2011111783A1 (en) * | 2010-03-12 | 2011-09-15 | カルピス株式会社 | Agent for controlling the increase and decrease of lactobacillus bifidus in colon |
| JP6302183B2 (en) * | 2013-07-12 | 2018-03-28 | 株式会社エンザミン研究所 | Adipocytokine production balance regulator, adipose tissue inflammation / oxidative stress inhibitor, and adipose tissue macrophage infiltration inhibitor |
| CN107073047B (en) * | 2014-10-28 | 2021-08-24 | 株式会社恩基美研究所 | insulin resistance improver |
| CN118638600A (en) * | 2022-03-24 | 2024-09-13 | 浙江省农业科学院 | Preparation equipment for probiotic composition with lipid-lowering effect |
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| JPH10234326A (en) * | 1997-02-26 | 1998-09-08 | Yusuke Sugaya | New processed soy foods |
| JP2000505308A (en) * | 1996-02-29 | 2000-05-09 | ニュートリ・ファーマ・アルメント・アクシェセルスカブ | Compositions and their use as food supplements or for lowering serum lipids |
| JP2002509891A (en) * | 1998-04-01 | 2002-04-02 | ガネデン バイオテック, インコーポレイテッド | Methods, systems, and compositions for reducing cholesterol using Bacilluscoagulans spores |
| JP2003524610A (en) * | 1998-11-25 | 2003-08-19 | ニュートリ・ファーマ・アルメント・アクシェセルスカブ | Composition comprising soy protein, dietary fiber and a phytoestrogen compound and its use in the prevention and / or treatment of type 2 diabetes, metabolic syndrome and related cardiovascular diseases |
| JP2005206545A (en) * | 2004-01-23 | 2005-08-04 | Kyoto Univ | Soybean-derived peptide mixture having lipid metabolism regulating action and use thereof |
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| JPS63209580A (en) * | 1987-02-25 | 1988-08-31 | Karupisu Shokuhin Kogyo Kk | Bacillus subtilis c-3102 |
| JPH0424022A (en) | 1990-05-21 | 1992-01-28 | Hitachi Medical Corp | Mobile x-ray apparatus |
| US5776756A (en) * | 1995-08-31 | 1998-07-07 | Toyo Hakko Co., Ltd. | Fermentation compositions having superoxide dismutating activity and an antihypertensive agent for treatment of constipation each having the superoxide dismutating activity |
| JP3489930B2 (en) * | 1996-03-08 | 2004-01-26 | 株式会社ヤクルト本社 | Cancer prevention food |
| US6811786B1 (en) * | 1999-04-01 | 2004-11-02 | Ganeden Biotech, Inc. | Methods for reducing cholesterol using Bacillus coagulans spores, systems and compositions |
| JP2004111573A (en) * | 2002-09-17 | 2004-04-08 | Sony Corp | Semiconductor device and method of manufacturing the same |
| JP4309108B2 (en) * | 2002-09-26 | 2009-08-05 | 大和薬品株式会社 | Diabetes medicine |
| JP4503951B2 (en) * | 2003-08-06 | 2010-07-14 | 株式会社琉球バイオリソース開発 | Diabetes disease prevention and treatment agent |
| JP2006111573A (en) * | 2004-10-14 | 2006-04-27 | Ee H C:Kk | Use of bacillus subtilis sp. and food containing the same to be used |
| JP2006151952A (en) | 2004-11-05 | 2006-06-15 | Oto Corporation:Kk | Hyperlipidemia or hyperuricemia improving agent and health food |
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- 2007-08-14 BR BRPI0715740A patent/BRPI0715740A8/en not_active IP Right Cessation
- 2007-08-14 US US12/438,242 patent/US20100183576A1/en not_active Abandoned
- 2007-08-14 WO PCT/JP2007/065848 patent/WO2008023608A1/en not_active Ceased
- 2007-08-14 KR KR1020097005822A patent/KR101454228B1/en not_active Expired - Fee Related
- 2007-08-14 CN CN2007800312533A patent/CN101511377B/en not_active Expired - Fee Related
- 2007-08-14 JP JP2008530867A patent/JP5113057B2/en active Active
- 2007-08-14 CA CA2661373A patent/CA2661373C/en not_active Expired - Fee Related
- 2007-08-14 EP EP07792491A patent/EP2060263A4/en not_active Withdrawn
- 2007-08-14 MX MX2009001782A patent/MX2009001782A/en active IP Right Grant
- 2007-08-20 TW TW096130744A patent/TW200817020A/en unknown
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2012
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2060263A1 (en) | 2009-05-20 |
| BRPI0715740A8 (en) | 2017-01-24 |
| KR101454228B1 (en) | 2014-10-23 |
| CN101511377B (en) | 2012-10-03 |
| KR20090059124A (en) | 2009-06-10 |
| US20100183576A1 (en) | 2010-07-22 |
| US20130017181A1 (en) | 2013-01-17 |
| TW200817020A (en) | 2008-04-16 |
| CA2661373A1 (en) | 2008-02-28 |
| CA2661373C (en) | 2014-10-07 |
| MX2009001782A (en) | 2009-02-25 |
| WO2008023608A1 (en) | 2008-02-28 |
| CN101511377A (en) | 2009-08-19 |
| JPWO2008023608A1 (en) | 2010-01-07 |
| BRPI0715740A2 (en) | 2013-07-16 |
| EP2060263A4 (en) | 2012-01-25 |
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